White adipose tissue (WAT) remodeling is an emerging therapeutic strategy for treatment of obesity-related disorders like diabetes. Remodeling of WAT by beta3 adrenergic activation is a robust model that allows mechanisms to be tested in vivo and in vitro. Using this model system, the progenitors of the brown adipocytes that appear in WAT were identified, and techniques for imaging, isolating, and genetically manipulating these cells in vivo were developed. These cells appear to act as adult 'remodeling stem cells'(rmSC) that are likely involved in the remodeling and cellular restoration of WAT under various conditions. This project will examine mechanisms by which these novel rmSC are recruited by WAT therapeutic remodeling and by chronic high fat feeding. The long term goal is to guide strategies for expanding metabolically desirable adipocyte phenotypes for treating obesity-related disorders.

Public Health Relevance

This project will examine mechanisms by which novel adult stem cells in white adipose tissue are recruited by therapeutic remodeling and by chronic high fat feeding. The long term goal is to guide strategies for expanding metabolically desirable adipocyte phenotypes for treating obesity-related disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK062292-08
Application #
8370098
Study Section
Cellular Aspects of Diabetes and Obesity Study Section (CADO)
Program Officer
Haft, Carol R
Project Start
2002-07-01
Project End
2017-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
8
Fiscal Year
2012
Total Cost
$330,600
Indirect Cost
$113,100
Name
Wayne State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001962224
City
Detroit
State
MI
Country
United States
Zip Code
48202
Lee, Yun-Hee; Kim, Sang-Nam; Kwon, Hyun-Jung et al. (2016) Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue. Am J Physiol Regul Integr Comp Physiol 310:R55-65
Gartung, Allison; Zhao, Jiawei; Chen, Simon et al. (2016) Characterization of Eicosanoids Produced by Adipocyte Lipolysis: IMPLICATION OF CYCLOOXYGENASE-2 IN ADIPOSE INFLAMMATION. J Biol Chem 291:16001-10
Lee, Yun-Hee; Petkova, Anelia P; Konkar, Anish A et al. (2015) Cellular origins of cold-induced brown adipocytes in adult mice. FASEB J 29:286-99
Granneman, J G (2015) Renaissance of brown adipose tissue research: integrating the old and new. Int J Obes Suppl 5:S7-S10
Sanders, Matthew A; Madoux, Franck; Mladenovic, Ljiljana et al. (2015) Endogenous and Synthetic ABHD5 Ligands Regulate ABHD5-Perilipin Interactions and Lipolysis in Fat and Muscle. Cell Metab 22:851-60
Mottillo, Emilio P; Paul, George M; Moore, Hsiao-Ping H et al. (2014) Use of fluorescence microscopy to probe intracellular lipolysis. Methods Enzymol 538:263-78
Mottillo, Emilio P; Balasubramanian, Priya; Lee, Yun-Hee et al. (2014) Coupling of lipolysis and de novo lipogenesis in brown, beige, and white adipose tissues during chronic β3-adrenergic receptor activation. J Lipid Res 55:2276-86
Lee, Yun-Hee; Mottillo, Emilio P; Granneman, James G (2014) Adipose tissue plasticity from WAT to BAT and in between. Biochim Biophys Acta 1842:358-69
Lee, Yun-Hee; Thacker, Robert I; Hall, Brian Eric et al. (2014) Exploring the activated adipogenic niche: interactions of macrophages and adipocyte progenitors. Cell Cycle 13:184-90
Contreras, G Andres; Lee, Yun-Hee; Mottillo, Emilio P et al. (2014) Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab 307:E793-9

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